Citation: Martinelli, G.; Angarano, M.; Piazza, S.; Fumagalli, M.; Magnavacca, A.; Pozzoli, C.; Khalilpour, S.; Dell’Agli, M.; Sangiovanni, E. The Nutraceutical Properties of Sumac (Rhus coriaria L.) against Gastritis: Antibacterial and Anti-Inflammatory Activities in Gastric Epithelial Cells Infected with H. pylori. Nutrients 2022, 14, 1757. https://doi.org/10.3390/ nu14091757 Academic Editors: Valentina Melini and Maurizio Ruzzi Received: 12 April 2022 Accepted: 20 April 2022 Published: 22 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article The Nutraceutical Properties of Sumac (Rhus coriaria L.) against Gastritis: Antibacterial and Anti-Inflammatory Activities in Gastric Epithelial Cells Infected with H. pylori Giulia Martinelli 1 , Marco Angarano 1 , Stefano Piazza 1, * , Marco Fumagalli 1 , Andrea Magnavacca 1 , Carola Pozzoli 1 , Saba Khalilpour 1,2,3 , Mario Dell’Agli 1 and Enrico Sangiovanni 1 1 Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; giulia.martinelli@unimi.it (G.M.); marco.angarano@guest.unimi.it (M.A.); marco.fumagalli3@unimi.it (M.F.); andrea.magnavacca@unimi.it (A.M.); carola.pozzoli@unimi.it (C.P.); skhalilpour@gmail.com (S.K.); mario.dellagli@unimi.it (M.D.); enrico.sangiovanni@unimi.it (E.S.) 2 Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02115, USA 3 Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA * Correspondence: stefano.piazza@unimi.it Abstract: Sumac (Rhus coriaria L.) is a spice and medicinal herb traditionally used in the Mediter- ranean region and the Middle East. Since we previously demonstrated Sumac biological activity in a model of tumor necrosis factor alpha (TNF-α)-induced skin inflammation, the present work is aimed at further demonstrating a potential role in inflammatory disorders, focusing on gastritis. For this purpose, different polar extracts (water-W, ethanol-water-EW, ethanol-E, ethanol macerated- Em, acetone-Ac, ethylacetate-EtA) were investigated in gastric epithelial cells (GES-1) challenged by TNF-α or H. pylori infection. The ethanolic extracts (E, EW, Em) showed the major phenolic contents, correlating with lower half maximal inhibitory concentrations (IC 50 s) on the release of interleukin-8 (IL-8, <15 μg/mL) and interleukin-6 (IL-6, <20 μg/mL) induced by TNF-α. Similarly, they inhibited IL-8 release (IC 50 s < 70 μg/mL) during Helicobacter pylori (H. pylori) infection and exhibited a direct antibacterial activity at comparable concentrations (minimum inhibitory concen- tration (MIC) = 100 μg/mL). The phenolic content and the bioactivity of EW were maintained after simulated gastric digestion and were associated with nuclear factor kappa B (NF-κB) impairment, considered the main putative anti-inflammatory mechanism. On the contrary, an anti-urease activity was excluded. To the best of our knowledge, this is the first demonstration of the potential role of Sumac as a nutraceutical useful in H. pylori-related gastritis. Keywords: Sumac; Rhus coriaria L.; gastritis; H. pylori; inflammation; nutraceuticals; botanicals 1. Introduction Rhus coriaria L. (Sumac) belongs to the Anacardiaceae family, widely grown throughout the Mediterranean region. Leaves and fruits have a remarkable medicinal value in Middle Eastern herbal medicine [1]. The brown/red fruits of Rhus coriaria are used as a very popular spice in food production for their sour lemony taste. Phytochemical characterization of berries showed the occurrence of different antioxidants belonging to several classes of polyphenols, among which flavonoids and gallotannins are the most abundant [2]. Red fruits are traditionally used in Persian medicine to treat diarrhea, hemorrhoids, gout, and decrease cholesterol, uric acid, and blood sugar levels, and for a variety of other biological activities recently revised by Elagbar et al. [1]. Much evidence supports the pharmacological and nutraceutical properties of Sumac in a variety of diseases [3–8]. Moreover, additional studies demonstrated interesting effects in inflammatory conditions, including the reduction of pro-inflammatory mediators and the inhibition of the nuclear factor kappa B (NF-κB) activation in human keratinocytes challenged with tumor necrosis factor alpha (TNF-α)[5]. Nutrients 2022, 14, 1757. https://doi.org/10.3390/nu14091757 https://www.mdpi.com/journal/nutrients